Virology Journal最新文献

Background: Geminiviruses represent a significant threat to global agriculture due to the substantial crop loss they inflict worldwide. Histone chaperones, a highly conserved family of proteins primarily recognized for their roles in nucleosome assembly and disassembly, have demonstrated crucial involvement in animal virus biology. However, their contribution to the process of plant virus infection remains largely uncharacterized. To address this knowledge gap, we aimed to elucidate the role of two major histone chaperones, the replication-coupled Fasciata2 (FAS2) and the replication-independent Histone regulator A (HIRA), in the pathogenesis of geminiviruses in Nicotiana benthamiana.

Methods: We investigated the influence of histone chaperones NbHIRA and NbFAS2 during Pepper leaf curl Bangladesh virus (PepLCBV) infection within a permissive host, N. benthamiana. We employed quantitative real-time PCR (qRT-PCR) to quantify gene expression levels, discontinuous sucrose gradient assay to analyse viral minichromosome assembly, and Chromatin immunoprecipitation (ChIP) to examine histone-DNA interactions. We also evaluated both active and repressive histone methylation marks on viral minichromosomes, providing crucial insight into the regulatory influence of NbHIRA and NbFAS2 on viral gene activity.

Results: Our findings indicate that downregulation of NbHIRA and NbFAS2 leads to an increase in virus transcript accumulation. The virus may utilize the elevated NbRAD51 levels in the knockdown plants, contributing to the increased viral load. Conversely, overexpression of both NbHIRA and NbFAS2 exerts a significant antiviral effect, resulting in the reduction of virus transcripts in both local as well as distal plant tissues. This observed decrease in viral titre linked to a high degree of compaction of virus minichromosomes. Concurrently, these compacted virus minichromosomes exhibit an increase in accumulation of repressive histone mark H3K9me2, rendering them less virulent compared to wild-type virus minichromosomes.

Conclusions: Overexpression of NbHIRA and NbFAS2 significantly boosts antiviral activity against geminivirus infections by altering the structure of virus minichromosomes. Consequently, these findings propose that targeting histone chaperones such as NbHIRA and NbFAS2 could offer a promising strategy for managing geminivirus-related infections in crop plants and agricultural applications.

Hepatitis E virus (HEV) causes viral hepatitis, posing a risk to vulnerable populations. Although swine are established reservoirs, the involvement of other animal species remains undefined. This study investigated 301 livers from naturally deceased European hedgehogs collected from wildlife centres (northern Italy), to determine their role in HEV transmission, spread and epidemiology, considering their proximity to urban areas. No positive samples were found by Real-time PCR, suggesting that hedgehogs play a marginal role in HEV epidemiology. Further studies are required to investigate other potential wild reservoirs to gain insight into HEV transmission dynamics, given the global impact of HEV-related diseases.

Parvovirus B19 is a non-enveloped DNA virus of the Parvoviridae family, which usually causes erythema infectiosum in children. Although rare in adults, this virus can cause severe complications, including encephalitis. We report a case of a 50-year-old male patient, previously healthy, who was admitted to the hospital with high fever, headache, nausea, vomiting, and rapidly progressing to impaired consciousness. The patient was intubated and placed on mechanical ventilation. A lumbar puncture was performed, which showed mild leukocytosis with normal protein and glucose levels, and negative cultures. Tests to exclude common causes of encephalitis such as HSV, Influenza, Dengue, and HIV were all negative. Brain magnetic resonance imaging revealed corpus callosum lesions, while electroencephalography showed diffuse theta slow waves. Multiplex Polymerase chain reaction (PCR) of the cerebrospinal fluid confirmed the diagnosis of Parvovirus B19 infection. The patient was treated empirically with empirical broad-spectrum antibiotics (meropenem and vancomycin) and supportive intensive care. After seven days, the patient made a complete recovery without neurological sequelae and was discharged in a stable condition. This report emphasizes that Parvovirus B19, although generally considered a benign agent in children, can cause encephalitis in healthy adults and should be considered in the differential diagnosis of encephalitis of unknown etiology.

Background: This research was motivated by the widespread use of oral antivirals during the Covid-19 pandemic and the remaining uncertainty regarding their effects on viral kinetics, which have rarely been studied in real-world population cohorts of this size.

Methods: We analysed 291,340 SARS-CoV-2 cycle threshold (CT) values from 113,399 non-hospitalized adult patients in Vienna (01/2022-05/2023), including 30,451 from 12,166 nirmatrelvir-ritonavir recipients, 27,959 from 10,752 molnupiravir recipients, and 232,930 from 90,481 untreated controls.

Results: Both antivirals initially caused a rapid increase in mean CT values. After completion of the 5-day treatment course, CT values declined in both antiviral groups, which was not observed in untreated individuals.

Conclusions: These findings provide population-level evidence on post-treatment viral kinetics of oral antivirals during the Omicron wave.

The spread of African Swine Fever (ASF) across much of the world is a profound challenge to both domestic and wild Suidae populations. While vaccine and countermeasure development for domestic swine are ongoing, the understanding of ASF within wildlife is limited. This gap in knowledge is largely due to the requirements of working with African Swine Fever Virus (ASFV) in high containment laboratories, the complexity of utilizing wildlife in these settings, and researcher access to non-native species. Researching the role of ASFV within wildlife primary cells, outside a vivarium, is currently limited by the need to utilize either terminal processing procedures, such as harvesting alveolar macrophages or bone marrow, or processes requiring large volumes of blood, such as peripheral blood mononuclear cell harvests. The limited availability and access restrictions of susceptible wildlife makes obtaining these samples difficult, especially when working with endangered wildlife species. Harvesting buffy coat fractions is independent of terminal methodologies and the need for large volumes of blood. A methodology to support ASFV replication has recently been demonstrated utilizing domestic swine blood derived buffy coat cells. Through establishing collaborations with zoological partners, we apply this methodology to small volumes of blood from an African Warthog, a known ASF susceptible species. These results demonstrate the value of such partnerships and how they may be utilized in the future to evaluate ASFV in wildlife derived cells in vitro.

Foot-and-Mouth Disease (FMD) causes substantial economic losses to the global livestock industry annually. Current vaccines inadequately prevent infection and transmission of Foot-and-Mouth Disease Virus (FMDV), highlighting the urgent need for FMDV mRNA vaccines with enhanced immunogenicity and safety. The immunogenicity of mRNA vaccines is largely determined by sequence design, particularly the optimization of untranslated regions (UTRs), which significantly enhance mRNA stability and promote efficient antigen expression. In this study, eight UTR sequences were designed and evaluated using the enhanced green fluorescent protein (EGFP) reporter gene. Results showed that EGFP-UTR3 and EGFP-UTR8 performed best in protein expression. Subsequent integration of UTR3 and UTR8 into FMDV P12A3C mRNA revealed that P12A3C-UTR8 consistently achieved higher antigen expression across multiple cell models, elicited robust humoral and cellular immune responses in mice, and provided protection comparable to conventional inactivated vaccines in guinea pigs, indicating that UTR8 is a highly promising regulatory element for vaccine applications. Sequence analysis revealed that beyond the previously reported influence of the 5' UTR secondary structure, the GC content of the 3' UTR is strongly associated with mRNA translation efficiency. These findings elucidate the intrinsic link between UTR structure and function and provide critical theoretical support for optimizing FMDV mRNA vaccine and advancing novel vaccine development.

Background: This study analyzed the results of seven respiratory pathogen tests to investigate their epidemiological characteristics in children and provide clinical evidence for the prevention and control of acute respiratory infections (ARIs) in the pediatric population of Shanghai.

Methods: The test results for the seven pathogens (influenza A virus (FLUA), influenza B virus (FLUB), parainfluenza virus (PIV), adenovirus (ADV), respiratory syncytial virus (RSV), Mycoplasma pneumoniae (MP) and Chlamydia pneumoniae (CP)) were collected from 40,606 pediatric patients exhibiting clear ARI symptoms at Shanghai Children's Medical Center, affiliated with Shanghai Jiao Tong University School of Medicine from January 2018 to December 2023 and retrospectively analyzed. Statistical analyses were conducted on positive detection rates, infection patterns, epidemic periods and variations based on sex and age.

Results: The overall positive detection rate for the seven respiratory pathogens was 22.57%. Compared with those in 2018, 2019 (pre-COVID-19) and 2023 (post-COVID-19), the rate significantly decreased during the pandemic period (2020-2022) (P*<0.05), with mono-infections (mostly due to RSV, MP and PIV) being predominant. The epidemic periods of several pathogens shifted significantly after the pandemic. ADV (2.33%) and MP (14.52%) showed the highest positive detection rates among children aged 3 to < 6 years and 6 to < 12 years, respectively. Additionally, FLUA (1.46%) and FLUB (0.59%) exhibited the lowest rates in children aged 0 to < 3 years, while PIV (5.11%) and RSV (9.88%) showing the highest rates in the same age range. Finally, the positive detection rate of MP was significantly higher in girls (6.93%) than in boys (6.18%) (P*<0.05).

Conclusions: The overall positive detection rate for the seven respiratory pathogens decreased significantly during the pandemic (2020-2022), with several pathogens showing notable shifts in their pre- and post-pandemic epidemic periods. MP, RSV and PIV were identified as the primary ARI-causing pathogens in children, and age- or sex-related differences also observed. This study enhances current understanding of the epidemiological characteristics of respiratory pathogen infections among children spanning the pre-, during, and post-COVID-19 periods, and provides critical insights for developing more effective prevention and control strategies in Pudong, Shanghai.

Merkel cell polyomavirus (MCPyV) has been identified as the causative agent of Merkel cell carcinoma, and its non-coding control region (NCCR) has been demonstrated to play a critical role in regulating viral transcription. While NCCR variants exist, their comparative impact on bidirectional promoter activity remains poorly characterized. The present study conducted an in vitro evaluation of bidirectional transcription levels of five major MCPyV NCCR types (I, IIa-1, IIa-2, IIb, IIc). The NCCRs were subsequently cloned into a bidirectional reporter vector, which expresses green (EGFP, early) and red (RFP, late) fluorescent proteins. Subsequent to transfection into HEK293 cells, promoter activity was quantitatively analyzed via fluorescence imaging and flow cytometry. Bioinformatic analysis revealed high sequence similarity (> 94%) among the five NCCRs and predicted conserved transcription factor binding sites. The results indicated that all the variants exhibited stronger late promoter activity compared with the early promoter activity (p < 0.01). These observations are in alignment with the established biology of MCPyV. However, no statistically significant differences in the early/late transcription ratio or overall fluorescence intensity were observed between the different NCCR types under these conditions. These findings suggest that the core promoter function is conserved among these major NCCR variants in this model system. This study provides a foundational comparison of MCPyV NCCR activity, highlighting the need for further investigation in more physiologically relevant models to understand how NCCR diversity may influence viral pathogenesis in vivo. Moreover, incorporating models of viral genome integration is essential to understand mechanism of MCPyV carcinogenesis and viral-host interaction.